1. Technical Field
The present invention relates to an organ perfusion apparatus, and more particularly, to a perfusion apparatus and method including chemical compositions for extending the preservation period of a donor organ which has been harvested for transplantation.
2. Discussion
It is estimated that one of every four patients listed for cardiac transplantation dies awaiting the availability of a suitable organ donor. While progress has been made for making more donor organs available, the development of successful techniques for donor heart preservation has not kept pace with the demand for cardiac transplantation. With improvements in patient survival and the development of new immunosuppressive agents, heart transplantation has become more feasible, making the problem of organ supply even more critical. Despite the acceptable clinical results obtained with the current donor organ and donor heart preservation techniques, one of the major challenges that remains is the current inability to safely preserve the donor heart for more than four hours. Extending the preservation period beyond four hours using current preservation techniques significantly increases the risk of failure during or after transplantation. This four hour limitation also restricts the geographic area from which donor hearts can be transported for successful transplantation.
Current donor organ preservation protocols utilize hypothermic arrest and storage in a chemical perfusate for maintaining the heart (non-beating) for up to four hours. However, these protocols utilize a variety of crystalloid-based cardioplegic solutions that do not completely protect the donor heart from myocardial damage resulting from ischemia and other reperfusion injuries. In addition to myocardial damage, ischemia and reperfusion may also cause coronary vascular endothelial and smooth muscle injury leading to coronary vasomotor dysfunction. (Ischemia is generally defined as an insufficient blood supply to the heart muscle.)
These current preservation techniques involve arresting the heart with a crystalloid-based cardioplegic solution and storing the heart on ice in the same solution until implantation. Techniques have also been developed for perfusing the heart with the storage solution in the hypothermic state. The heart can then be transported in this hypothermic state for up to four hours until implantation. The most common cardioplegic preservation solutions used are The University of Wisconsin Solution (UW), St. Thomas Solution, and the Stanford University Solution (SU). However, all of the protocols utilizing these solutions require hypothermic arrest, and do not overcome the problems of myocardial damage.
As is well known in the art, for optimal donor heart preservation, the following principles apply: a) Minimization of cell swelling and edema; b) prevention of intracellular acidosis; c) prevention of injury caused by oxygen free radicals; and d) provision of substrate for regeneration of high-energy phosphate compounds and ATP during reperfusion. The current method of hypothermic arrest and storage preservation has been shown to result in cell swelling, intra- and extracellular acidosis, and a degradation of high-energy phosphates. Moreover, studies in humans have clearly demonstrated significant endothelial dysfunction following donor heart preservation when utilizing hypothermic arrest and storage protocols. In some instances, an organ which has undergone hypothermic arrest is transplanted into the recipient and cannot be restarted after transplantation. Many times, this is a result of acute graft failure at one or more locations on the heart. The problem of acute graft failure then requires constant support of the recipient's circulatory system by ventricular assist devices and/or cardiopulmonary bypass until a new donor heart can be located. In some instances, a suitable organ cannot be located in time which results in the death of the recipient. There is also increasing evidence from a number of recent clinical studies that the preservation of metabolic, contractile and vasomotor function is not optimal with current preservation protocols.
Based upon experimental studies, donor blood perfusate has been shown to be a more suitable alternative for clinical donor heart preservation because it provides better substrate, oxygen delivery, endogenous-free radical scavengers, potent buffers, and improved oncotic pressure. Accordingly, it is desirable to achieve prolonged ex-vivo preservation of the donor heart that has been harvested by providing continuous sanguineous perfusion, while maintaining the donor heart in the normal beating state. Such a technique would eliminate the need to arrest the heart for storage in a hypothermic environment, and overcome many of the problems associated with hypothermic arrest and storage.
Therefore, it is further desirable to provide an apparatus and method for creating an extracorporeal circuit for sanguineously perfusing the harvested organ at normothermia for preserving the harvested organ for up to twenty-four hours or longer. Such an apparatus and method would optimally maintain the harvested organ in the beating state during the preservation period to insure pulsatile coronary flow and homogeneous distribution of the substrate. Such an apparatus would also provide the ability to extend the preservation period of the harvested organ beyond the current four hour limit, while avoiding prolonged ischemia, preserving coronary endothelial vasomotor function, and preventing the metabolic degradation of high-energy phosphates.
Additionally, such an apparatus and method would allow for expanding the organ donor pool, increasing the histocompatibility matching time, and potentially reducing the incidents of cardiac allograft vasculopathy. Prolonging the preservation period of the donor heart would have a dramatic impact on the practice of heart transplantation. A worldwide retrieval of organs would be made possible, thus increasing the pool of available organs. Organs would not go unused because of lack of suitable nearby recipients. Moreover, additional time would become available to determine the immunologic and functional characteristics of each organ, thereby reducing the risk of graft failure.